Corticotrophin releasing factor (CRF) induced reinstatement of cocaine seeking in male and female rats

Abstract

Significant sex differences have been demonstrated in clinical and preclinical studies of cocaine addiction, with some of the most consistent differences noted in regard to the role of stress and craving. The current study examined stress-induced reinstatement of cocaine seeking in male and female rats in an animal model of relapse using corticotropin-releasing factor (CRF) administration. Both male and female rats demonstrated increased cocaine seeking in response to CRF. CRF-induced reinstatement was highly variable across both male and female rats, and further analysis revealed a subpopulation that was particularly sensitive to CRF (high responders). Female high responders displayed significantly increased responding to CRF compared to males. Individual differences in stress responsivity could thus contribute to the likelihood of relapse, with females showing greater heterogeneity to stress-induced relapse.

Figure 1

Active lever responding in males and females during cocaine self-administration (top) and extinction (bottom). Significant differences (*p<0.05) are noted for self-administration days 1–2 relative to self-administration days 3–10, and extinction day 1 relative to extinction days 2–7.

Figure 2

Active lever responses in males and females for the last day of extinction before testing (Ext) and on CRF-induced reinstatement tests for all subjects (top) or in high responders (bottom). Significant differences are noted for responding over extinction (*p<0.05) and for females relative to males (†p<0.05).